Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Infant formulas have been developed for these situations.
In the recent past, certain strains of bacteria have attracted considerable attention because they have been found to exhibit valuable properties for man if ingested. In particular, specific strains of the genera Lactobacilli and Bifidobacteria have been found to be able to colonise the intestinal mucosa, to reduce the capability of pathogenic bacteria to adhere to the intestinal epithelium, to have immunomodulatory effects and to assist in the maintenance of well-being. Such bacteria are sometimes called probiotics and it has already been proposed to add suitable probiotic bacteria to infant formulas.
Extensive studies have been carried out to identify new probiotic strains. For example, EP 0 199 535, EP 0 768 375, WO 97/00078, EP 0 577 903 and WO 00/53200 disclose specific strains of Lactobacilli and Bifidobacteria and their beneficial effects.
As indicated above, by reason of their abilities to colonise the intestinal mucosa and reduce the capacity of pathogenic bacteria to adhere to the intestinal epithelium, certain probiotic strains have already been proposed for the prevention and treatment of diarrhoea in infants. For example, Lactobacillus rhamnosus ATCC 53103 which is sold inter alia by Valio Oy of Finland under the trade mark LGG has been reported to be effective in reducing bacterially-induced diarrhoea in infants and young children (Canani et al, British Medical Journal 2007, Aug. 18; 335 (7615):340). commonly added to human foods, such as fermented milk products.
Another approach to preventing or treating infection of the gastrointestinal tract with bacterial pathogens such as Escherichia coli (EPEC) is the administration of prebiotics, for example by addition to foodstuffs. A prebiotic is a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Such ingredients are non-digestible in the sense that they are not broken down and absorbed in the stomach or small intestine and thus pass intact to the colon where they are selectively fermented by the beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS). Shoaf et al investigated the ability of various prebiotics including fructooligosaccharides, inulin, galacto-oligosaccharides, lactulose and raffinose to inhibit the attachment of EPEC strain E2348/69 on Hep-2 and Caco-2 cells. They observed that purified galacto-oligosaccharides exhibited the greatest adherence inhibition on both HEp-2 and Caco-2 cells, reducing the adherence of EPEC by 65 and 70%, respectively and concluded that their observations suggested that some prebiotic oligosaccharides may have anti-adhesive activity and directly inhibit the adherence of pathogens to the host epithelial cell surface (Infect Immun 2006 December; 74 (12): 6920-8).
Human milk is known to contain a larger amount of indigestible oligosaccharides than most other animal milks. In fact, indigestible oligosaccharides represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 12-15 g/l in colostrum and 5-8 g/l in mature milk. Human milk oligosaccharides are very resistant to enzymatic hydrolysis, indicating that these oligosaccharides may display essential functions not directly related to their calorific value.
As the composition of human milk becomes better understood, it has also been proposed to add prebiotics to infant formula. Various infant formulas supplemented with prebiotics such as mixtures of fructooligosaccharides and galactooligosaccharides for example are commercially available. However, such mixtures approximate only roughly the mixture of oligosaccharides in human milk. Over 100 different oligosaccharide components have been detected in human milk some of which have not been so far detected in animal milks such as bovine milk at all or have been detected only in small quantities. Examples of classes of human milk oligosaccharide that are present in bovine milk and colostrum only in very small quantities or not at all are sialylated and fucosylated oligosaccharides.
The number and function of these various oligosaccharides are still being elucidated although certain of them have also been associated with reducing the ability of pathogens to adhere to host epithelial cells. For example, Cravioto et al reported that an oligosaccharide-enriched fraction from human milk inhibited the attachment of EPEC to HEp-2 cells (The Journal of Infectious Diseases 1991; 163:1247-1255).
Infant formulas containing both probiotics and prebiotics have also been proposed in the continual quest to produce infant formulas which replicate as closely as possible the composition and efficacy of human milk. For example, in WO 2007/101675 it is proposed to supplement infant formula with a mixture of a probiotic bacterial strain and a mixture of N-acetylated, neutral and sialylated oligosaccharides which mixture provides a closer approximation to the oligosaccharides in human milk than does the commercially available mixtures of fructo- and galacto-oligosaccharides described above. It is stated that this mixture, which is described as a symbiotic, is useful for the prevention of pathogenic infections.
However, there is a continuing need to still further improve the protective effects of infant formulas and the like compositions by combining specific probiotics and prebiotics with particularly beneficial effects.